Proteomics study yields clues as to how tuberculosis might be thwarting the imm... (zzi and Keasling were Leslie Sheu Jun Li...)

Proteomics study yields clues as to how tuberculosis might be thwarting the immune system

Date:11/5/2008

zzi and Keasling were Leslie Sheu, Jun Liuc, Brian Smart, Christopher Petzold, Tsung-yen Hsieh and Austin Pitcher. Bertozzi and Keasling are also professors at the University of California at Berkeley. In addition, Bertozzi is an investigator with the Howard Hughes Medical Institute, and Keasling is director of the Joint BioEnergy Institute.

When bacteria or other foreign particles invade the body, the first line of defense are the macrophages, which engulf and contain the invaders within the membrane-bound shells of their phagosomes. Once safely contained, the invaders can be killed with digestive enzymes from another cell organelle, called a lysosome, which fuses with the phagosome. Macrophages, like other kinds of cells, also use lysosomal enzymes for internal housekeeping. However, until now there has been no direct biochemical evidence of a link between phagocytosis and autophagy.

Working with latex bead-containing phagosomes isolated in cell lines from mice, Shui and her colleagues performed a detailed analysis of the protein contents of the phagosomal membrane. Unlike earlier proteomic studies, which profiled the entire organelle and focused on abundant water-soluble protein species, the study by the Bertozzi-Keasling groups was membrane-specific and included hydrophobic protein species that are present in the membrane in relatively low amounts.

"We were able to demonstrate the endogenous level of LC3-II in macrophage phagosomes through the combination of sensitive proteomic techniques and biochemical assays," said Shui. "This is an excellent show-case of how a non-biased high-throughput proteomic study can shed new light on the diverse functions and pathways an organelle may engage in."

The LC3-II protein is a critical component of the autophagy machinery and the discovery that the level of its presence in phagosomes is modulated by autophagic activity (along with several other newly identified phagosome proteins not pre
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Contact: Lynn Yarris
lcyarris@lbl.gov
510-486-5375
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert

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Proteomics study yields clues as to how tuberculosis might be thwarting the imm...(zzi and Keasling were Leslie Sheu Jun Li...)